IKK[beta] Deficiency Causes Oxidative Stress and Prolonged JNK Activation Induced by Arsenic

Details

• Personal Author:
  Castranova, Vincent ; Chen F ; Karin M ; Li ZW ; Shi XL
• Description:
  Stress signals activate both IkB kinase (IKK) and c-Jun-Nterminal kinase (JNK), Recently, it was shown that IKK dependent NF-kB activation results in attenuation of TNFalpha-induced JNK activation. How that negative cross-talk between NF-kB and JNK occurs is not well-understood. By using wild type (WT) and Ikkbeta gene knockout (lkkB-/- ) mouse embryo fibroblasts (MEFs), we found that IKKB deficiency results in prolongation of arsenic-induced JNK activation, which was not due to the decreased expression of GADD45B or XIAP. as previously suggested for ReIA -/- cells treated with TNFalpha. This enhanced JNK activation was largely associated with an oxidative stress response as indicated by elevated expression of heme oxygenase-l and the accumulation of H2O2 in IkkB-/- cells. Expression profiling experiments revealed an increased expression of p450 family CYP1B1 mRNA in IkkB-/- cells compared to WT cells. Inhibition of CYP1B1 reduced both oxidative stress and arsenic-stimulated JNK activation. Thus, increased CYP1B1 expression is central to and seems to be responsible for sensitizing IkkB-/- cells to stress-induced JNK activation. [Description provided by NIOSH]
• Subjects:
  Animals Arsenic Biochemistry Genetics Inorganic Chemicals Laboratories Occupational Health Safety
• Keywords:
  Animal-studies Arsenic-compounds Biochemical-analysis Cell-function Cellular-reactions Genes Hydroperoxides Laboratory-animals Molecular-biology Oxidative-processes
• ISSN:
  0891-5849
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  35
• NIOSHTIC Number:
  nn:20032105
• Citation:
  Free Radic Biol Med 2003 Nov; 35(Suppl 1):S61-S62
• Contact Point Address:
  National Institute for Occupational Safety and Health, Health Effects Laboratory Division, Pathology and Physiological Research Branch, 1095 Willowdale Road, Morgantown, WV 26505
• CAS Registry Number:
  Arsenic (CAS RN 7440-38-2) ; Hydrogen peroxide (CAS RN 7722-84-1)
• Federal Fiscal Year:
  2004
• Peer Reviewed:
  False
• Source Full Name:
  Free Radical Biology and Medicine
• Supplement:
  1
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2193f71100c85fa541a6c197bea5297f5d858351659eaa7bbe8392c5d9e5ad77ca43af4e903943fd456b4a0fbdd9930a16a28247c79ae0fad5f04e0e9084ee60
• Download URL:
  https://stacks.cdc.gov/view/cdc/186157/cdc_186157_DS1.pdf
• File Type:
  [PDF - 4.17 MB ]